The effect of bisphenol a exposure onto endothelial and decidualized stromal cells on regulation of the invasion ability of trophoblastic spheroids in in vitro co-culture model

Bisphenol A (BPA) is a kind of environmental endocrine disruptors (EEDs) that interfere embryo implantation. Trophoblast invasion plays a crucial role during embryo implantation. In this study, the effects of BPA on invasion ability of human trophoblastic Jeg-3 spheroids and regulation of endothelial and stromal cells on trophoblastic spheroids invasion, and its possible mechanism were investigated. The results showed that BPA at 10 and 100 μM can inhibit the attachment of Jeg-3 spheroid onto Ishikawa cells. BPA at 1–100 μM also activate ERE-Luc reporter expression in the transfected cells, which was through the ERα, but not ERβ or GPR30 binding. Endothelial receptivity ability was harmed by BPA treatment since receptivity markers of LIF, EGF, MUC1 and integrin αVβ3 were decreased after BPA treatment. The invasion ability of trophoblastic spheroids generated from Jeg-3 cell line was inhibited by BPA and this effect was mediated through canonical ERs pathway and MMP2/MMP9 down-regulation and TIMP1/PAI-1 up-regulation. Besides, BPA treated decidualized stromal cells suppressed Jeg-3 spheroid outgrowth and invasion in co-culture assay. Our study would give a better understanding on the possible mechanism of BPA effect on human embryo implantation process. •High concentrations of BPA reduced Ishikawa cell proliferation and viability.•Spheroids attachment rate was decreased by BPA.•BPA decreased Jeg-3 spheroid outgrowth and invasion through ERs pathway.•BPA inhibited the outgrowth and invasion of trophoblast spheroids on decidualized stromal cells.